nemtabrutinib   Click here for help

GtoPdb Ligand ID: 11413

Synonyms: ARQ-531 | ARQ531 | ArQule 531 | MK-1026 | MK1026
PDB Ligand
Compound class: Synthetic organic
Comment: Nemtabrutinib (ARQ-531) is a reversible, ATP-competitive kinase inhibitor, that was originally designed to inhibit Bruton tyrosine kinase (BTK) [2]. It does not interact with BTK's catalytic domain Cys481 so may not be susceptible to resistance conferred by mutation of this residue. This is in contrast to ibrutinib, which is sensitive to alterations at Cys481. Nemtabrutinib has inhibitory activities against a range of other TEC family kinases, as well as Src and Trk kinases [1-2]. This non-selective activity is believed to contribute to nemtabrutinib's efficacy against chronic lymphocytic leukemia cells.
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2D Structure
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Physico-chemical Properties
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Hydrogen bond acceptors 6
Hydrogen bond donors 3
Rotatable bonds 7
Topological polar surface area 109.36
Molecular weight 478.14
XLogP 4.67
No. Lipinski's rules broken 0
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Canonical SMILES OC[C@@H]1CC[C@H](CO1)Nc1ncnc2c1c(c[nH]2)C(=O)c1ccc(cc1Cl)Oc1ccccc1
Isomeric SMILES OC[C@@H]1CC[C@H](CO1)Nc1ncnc2c1c(c[nH]2)C(=O)c1ccc(cc1Cl)Oc1ccccc1
InChI InChI=1S/C25H23ClN4O4/c26-21-10-17(34-16-4-2-1-3-5-16)8-9-19(21)23(32)20-11-27-24-22(20)25(29-14-28-24)30-15-6-7-18(12-31)33-13-15/h1-5,8-11,14-15,18,31H,6-7,12-13H2,(H2,27,28,29,30)/t15-,18+/m1/s1
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Summary of Clinical Use Click here for help
Nemtabrutinib (ARQ-531) is under evaluation for efficacy in hematologic malignancies (max phase 2 in Feb. 2021).
Clinical Trials
Clinical Trial ID Title Type Source Comment References
NCT03162536 A Study of ARQ 531 in Patients With Selected Hematologic Malignancies Phase 1/Phase 2 Interventional ArQule
NCT04728893 Efficacy and Safety of MK-1026 in Participants With Hematologic Malignancies (MK-1026-003) Phase 2 Interventional Merck Sharp & Dohme Corp.